tbuckley/cabot-search huggingface dataset:
A call to review values, commitment, and outlook to mainstream mental health
Authors: Manasi Kumar, André J van Rensburg, Inge Petersen
Journal: The Lancet Global Health (2023)

Mental health cannot succeed within integrated and holistic care solely through the efforts of those who work in mental health. The need to mainstream mental health within global health is thus axiomatic. While there are shifts in this direction, mental health remains mostly an add-on in global health programmes. Layering mental health into global health efforts in low- and middle-income countries (LMICs) is further beset with many challenges related to the neo-colonialist agenda of global health.
Association between First Trimester Exposure to Ambient PM2.5 and NO2 and Congenital Heart Defects: A Population-Based Cohort Study of 1,342,198 Live Births in Canada
Authors: Stéphane Buteau, Paige Veira, Marianne Bilodeau-Bertrand, Nathalie Auger
Journal: Environmental Health Perspectives (2023)

Background: The extent to which ambient air pollution contributes to the pathogenesis of congenital heart defects remains uncertain. Objective: We investigated whether first trimester exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) was associated with the risk of critical and noncritical heart defects in a large population-based cohort of births. Methods: We carried out a retrospective cohort study of children conceived between 2000 and 2016 in Quebec, Canada. Heart defects were identified via data from the Maintenance and Use of Data for the Study of Hospital Clientele registry. The main exposures were average concentration of PM2.5 and NO2 in a) the first trimester and b) the month of conception. Exposures were estimated at the residential postal code. Associations with critical and noncritical heart defects were assessed using logistic regression models, adjusted for maternal and infant characteristics. We considered single- and two-pollutant models and assessed modifying effects of maternal comorbidity, including preexisting hypertension, preeclampsia, anemia, and diabetes. Results: The cohort comprised 1,342,198 newborns, including 12,715 with heart defects. Exposure in the first trimester and month of conception yielded similar results; both were associated with a greater risk of heart defects. Adjusted odds ratios (OR) for any heart defect per interquartile range increase were 1.02 (95% CI: 1.00, 1.05) for PM2.5 and 1.10 (95% CI: 1.07, 1.13) for NO2. Associations with atrial septal defects were 1.08 (95% CI: 1.03, 1.14) for PM2.5 and 1.19 (95% CI: 1.12, 1.25) for NO2. Corresponding ORs for ventricular septal defects and individual critical heart defects were not significant. PM2.5 (OR=1.11; 95% CI: 1.06, 1.17) and NO2 (OR=1.23; 95% CI: 1.17, 1.31) exposure were associated with a greater risk of heart defects in mothers with comorbidity. Discussion: In this population-based cohort, prenatal exposure to ambient air pollution during the first trimester was associated with an increased risk of heart defects, particularly atrial septal defects. The association with heart defects was greater in mothers with comorbidity. https://doi.org/10.1289/EHP11120
Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study
Authors: Brian D Nicholson, Jason Oke, Pradeep S Virdee, Dean A Harris, Catherine O'Doherty, John ES Park, Zaed Hamady, Vinay Sehgal, Andrew Millar, Louise Medley, Sharon Tonner, Monika Vargova, Lazarina Engonidou, Kaveh Riahi, Ying Luan, Sara Hiom, Harpal Kumar, Harit Nandani, Kathryn N Kurtzman, Ly-Mee Yu, Clare Freestone, Sarah Pearson, FD Richard Hobbs, Rafael Perera, Mark R Middleton
Journal: The Lancet Oncology (2023)

Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care.
Sex specific molecular networks and key drivers of Alzheimer’s disease
Authors: Lei Guo, Jiqing Cao, Jianwei Hou, Yonghe Li, Min Huang, Li Zhu, Larry Zhang, Yeji Lee, Mariana Lemos Duarte, Xianxiao Zhou, Minghui Wang, Chia-Chen Liu, Yuka Martens, Michael Chao, Alison Goate, Guojun Bu, Vahram Haroutunian, Dongming Cai, Bin Zhang
Journal: Molecular Neurodegeneration (2023)

Alzheimer's disease (AD) is a progressive and age-associated neurodegenerative disorder that affects women disproportionally. However, the underlying mechanisms are poorly characterized. Moreover, while the interplay between sex and ApoE genotype in AD has been investigated, multi-omics studies to understand this interaction are limited. Therefore, we applied systems biology approaches to investigate sex-specific molecular networks of AD.We integrated large-scale human postmortem brain transcriptomic data of AD from two cohorts (MSBB and ROSMAP) via multiscale network analysis and identified key drivers with sexually dimorphic expression patterns and/or different responses to APOE genotypes between sexes. The expression patterns and functional relevance of the top sex-specific network driver of AD were further investigated using postmortem human brain samples and gene perturbation experiments in AD mouse models.Gene expression changes in AD versus control were identified for each sex. Gene co-expression networks were constructed for each sex to identify AD-associated co-expressed gene modules shared by males and females or specific to each sex. Key network regulators were further identified as potential drivers of sex differences in AD development. LRP10 was identified as a top driver of the sex differences in AD pathogenesis and manifestation. Changes of LRP10 expression at the mRNA and protein levels were further validated in human AD brain samples. Gene perturbation experiments in EFAD mouse models demonstrated that LRP10 differentially affected cognitive function and AD pathology in sex- and APOE genotype-specific manners. A comprehensive mapping of brain cells in LRP10 over-expressed (OE) female E4FAD mice suggested neurons and microglia as the most affected cell populations. The female-specific targets of LRP10 identified from the single cell RNA-sequencing (scRNA-seq) data of the LRP10 OE E4FAD mouse brains were significantly enriched in the LRP10-centered subnetworks in female AD subjects, validating LRP10 as a key network regulator of AD in females. Eight LRP10 binding partners were identified by the yeast two-hybrid system screening, and LRP10 over-expression reduced the association of LRP10 with one binding partner CD34.These findings provide insights into key mechanisms mediating sex differences in AD pathogenesis and will facilitate the development of sex- and APOE genotype-specific therapies for AD.
How to Treat Diffuse Large B-Cell Lymphoma
Authors: Swetha Kambhampati Thiruvengadam, Alex F. Herrera, June-Wha Rhee
Journal: JACC CardioOncology (2023)

Anthracycline-containing therapy is the cornerstone of frontline treatment for diffuse large B-cell lymphoma (DLBCL), and autologous stem cell transplantation, and more recently, chimeric antigen receptor T-cell therapy are the primary treatment options for relapsed refractory DLBCL. Given these therapies are all associated with cardiovascular toxicities, patients with underlying cardiac comorbidities are severely limited in treatment options. The focus of this review is to outline the cardiotoxicities associated with these standard treatments, explore strategies developed to mitigate these toxicities, and review novel treatment strategies for patients with underlying cardiovascular comorbidities. DLBCL patients with underlying cardiac complications are a high-risk patient population who require complicated management strategies that utilize a multidisciplinary approach with collaboration between cardiologists and oncologists.
Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion
Authors: Eric T Ahrens, Brooke M Helfer, Charles F O’Hanlon, Deanne R Lister, Julie L Bykowski, Karen Messer, Benjamin I Leach, Jiawen Chen, Hongyan Xu, Gregory A Daniels, Ezra E W Cohen
Journal: Journal for ImmunoTherapy of Cancer (2023)

Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF. Autologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant. We show that it is feasible to PFC-label ~70×1010 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer. Survival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.
Organoids as a tool in drug discovery and patient-specific therapy for head and neck cancer
Authors: Aaron J. Done, Andrew C. Birkeland
Journal: Cell Reports Medicine (2023)

Organoids more accurately reflect tumor microenvironment than traditional models. Millen et al. demonstrated organoids replicated from patient tissues may predict patient-specific response to radiation therapy and have potential to be utilized for validation of biomarkers in drug discovery and treatment planning.
Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment
Authors: Leonard C. Rogers, Jeff C. Kremer, Caitlyn B. Brashears, Zongtao Lin, Zhixian Hu, Alliny C.S. Bastos, Adriana Baker, Nicole Fettig, Dong Zhou, Kooresh I. Shoghi, Carina A. Dehner, John S.A. Chrisinger, John S. Bomalaski, Benjamin A. Garcia, Toshinao Oyama, Eileen P. White, Brian A. Van Tine
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 reexpression. This study examines the role of ASS1 silencing on tumor growth and initiation and identifies a noncanonical mechanism of resistance, aiming to improve clinical responses to ADI-PEG20. Experimental Design: Tumor initiation and growth rates were measured for a spontaneous Ass1 knockout (KO) murine sarcoma model. Tumor cell lines were generated, and resistance to arginine deprivation therapy was studied in vitro and in vivo. Results: Conditional Ass1 KO affected neither tumor initiation nor growth rates in a sarcoma model, contradicting the prevalent idea that ASS1 silencing confers a proliferative advantage. Ass1 KO cells grew robustly through arginine starvation in vivo, while ADI-PEG20 remained completely lethal in vitro, evidence that pointed toward a novel mechanism of resistance mediated by the microenvironment. Coculture with Ass1-competent fibroblasts rescued growth through macropinocytosis of vesicles and/or cell fragments, followed by recycling of protein-bound arginine through autophagy/lysosomal degradation. Inhibition of either macropinocytosis or autophagy/lysosomal degradation abrogated this growth support effect in vitro and in vivo. Conclusions: Noncanonical, ASS1-independent tumor resistance to ADI-PEG20 is driven by the microenvironment. This mechanism can be targeted by either the macropinocytosis inhibitor imipramine or the autophagy inhibitor chloroquine. These safe, widely available drugs should be added to current clinical trials to overcome microenvironmental arginine support of tumors and improve patient outcomes.
Sustainability of a 12-month lifestyle intervention delivered by community health workers in reducing blood pressure in Nepal: 5-year follow-up of the COBIN open-label, cluster randomised trial
Authors: Rajshree Thapa, Ayse Zengin, Dinesh Neupane, Shiva Raj Mishra, Sweta Koirala, Per Kallestrup, Amanda G Thrift
Journal: The Lancet Global Health (2023)

The sustainability and scalability of limited-duration interventions in low-income and middle-income countries remain unclear. We aimed to investigate the sustainability in reduction of blood pressure through a 12-month lifestyle intervention led by community health workers to reduce blood pressure in Nepal, 4 years after the intervention ceased.
The way forward in decolonising global health
Authors: Sudeep Adhikari, Irene Torres, Elizabeth Oele
Journal: The Lancet Global Health (2023)

The Lancet Global Health has taken steps towards listening to and platforming the voices of low-income and middle-income country (LMIC) authors, such as its 2021 call for papers on the topic of "what is wrong with global health?" In this issue—marking the journal's tenth anniversary—the journal gave editorial responsibility to a panel of LMIC-based guest editors. We (the guest editors) selected content for this issue on "The future of global health research, publishing, and practice", which was invited in the February issue editorial.
Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective
Authors: Fanny M. Elahi, Suvarna Alladi, Sandra E. Black, Jurgen A.H.R. Claassen, Charles DeCarli, Timothy M. Hughes, Justine Moonen, Nicholas M. Pajewski, Brittani R. Price, Claudia Satizabal, C. Elizabeth Shaaban, Nárlon C.B.S. Silva, Heather M. Snyder, Lukas Sveikata, Jeff D. Williamson, Frank J. Wolters, Atticus H. Hainsworth
Journal: Cell Reports Medicine (2023)

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND.Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.
The genesis of human hematopoietic stem cells
Authors: Vincenzo Calvanese, Hanna K. A. Mikkola
Journal: Blood (2023)

Developmental hematopoiesis consists of multiple, partially overlapping hematopoietic waves that generate the differentiated blood cells required for embryonic development while establishing a pool of undifferentiated hematopoietic stem cells (HSCs) for postnatal life. This multilayered design in which active hematopoiesis migrates through diverse extra and intraembryonic tissues has made it difficult to define a roadmap for generating HSCs vs non-self-renewing progenitors, especially in humans. Recent single-cell studies have helped in identifying the rare human HSCs at stages when functional assays are unsuitable for distinguishing them from progenitors. This approach has made it possible to track the origin of human HSCs to the unique type of arterial endothelium in the aorta-gonad-mesonephros region and document novel benchmarks for HSC migration and maturation in the conceptus. These studies have delivered new insights into the intricate process of HSC generation and provided tools to inform the in vitro efforts to replicate the physiological developmental journey from pluripotent stem cells via distinct mesodermal and endothelial intermediates to HSCs.
Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal
Authors: Anne Gompel, Cynthia A. Stuenkel
Journal: Cell Reports Medicine (2023)

Fezolinetant is a neurokinin 3 receptor antagonist under investigation for treatment of menopausal symptoms. In a recent study, Lederman and colleagues1 reported the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.
AL AMYLOIDOSIS UPFRONT TREATMENT AND CURRENT AND FUTURE STUDIES
Authors: E. Kastritis
Journal: HemaSphere (2023)

The treatment of AL amyloidosis is based on the elimination of the plasma cell clone. Today, approved therapies include combinations of the anti-CD38 monoclonal antibody daratumumab with bortezomib, cyclophosphamide and dexamethasone (D-VCd); this combination is effective with about 50%-60% of the patients achieving complete hematologic response and about 80% achieving at least a very good partial hematologic response. However, there are still several unmet needs: patients with very advanced cardiac amyloidosis, such as those stage 3B disease, have been excluded from the clinical trials, and they still have a very poor outcome. Second, at least 50% of patients with AL amyloidosis still fails to achieve a clinically significant organ function improvement. Finally, for patients failing to achieve hematologic or organ response or those who relapse after initial response, there is a need for new treatments and novel strategies. Although most treatments for patients with AL amyloidosis come from the myeloma field, not every therapy given for myeloma is suitable for patients with AL amyloidosis. Targeted therapies, such as those targeting BCL2, can be quite effective, since about 50% of AL patients harbor t(11;14). Anti-BCMA targeting therapies are also promising but they need to be further explored in the setting of AL amyloidosis. Experience with cellular therapies and T-cell redirecting therapies is still limited in AL amyloidosis; such therapies could be quite effective in eliminating the small but toxic amyloidogenic plasma cell clone but their toxicity should be explored specifically in patients with AL amyloidosis. An urgent need remains for the treatment of patients with very advanced cardiac involvement, for which even a deep hematologic remission may not be enough. For these patients, regimens with low toxicity and high efficacy should be prioritized and combined with potentially active amyloid targeting therapies. Combinations of non-cardiotoxic, non-nephrotoxic and non-neurotoxic agents should be prioritized, preferably in fixed duration regimens.
What Role for New York Heart Association Class in Heart Failure Clinical Trials?
Authors: Felix Lindberg, Daniela Tomasoni, Gianluigi Savarese
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Comparative Effectiveness of Percutaneous Microaxial Left Ventricular Assist Device vs Intra-Aortic Balloon Pump or No Mechanical Circulatory Support in Patients With Cardiogenic Shock
Authors: Zaid I. Almarzooq, Yang Song, Issa J. Dahabreh, Ajar Kochar, Enrico G. Ferro, Eric A. Secemsky, Jacqueline M. Major, Andrew Farb, Changfu Wu, Bram Zuckerman, Robert W. Yeh
Journal: JAMA Cardiology (2023)

Recent studies have produced inconsistent findings regarding the outcomes of the percutaneous microaxial left ventricular assist device (LVAD) during acute myocardial infarction with cardiogenic shock (AMICS).
Ambroxol as Therapy for Gaucher Disease—Ambitious but Ambivalent
Authors: Neal J. Weinreb, Ozlem Goker-Alpan
Journal: JAMA Network Open (2023)

Xia Zhan, MM; Huiwen Zhang, MD, PhD; Gustavo H. B. Maegawa, MD, PhD; Yu Wang, BM; Xiaolan Gao, BM; Dengbin Wang, MD, PhD; Jinning Li, MD, PhD
Comments on Study About Bariatric Surgery and Gastroesophageal Cancer
Authors: Sheng-Yin Chen, Chuan Lu, Tobias Kurth
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal